This document summarizes a new treatment for cancer-induced bone diseases called MBC-11 Compound. MBC-11 is a conjugate of a bisphosphonate (which targets bone) and a cytotoxic agent. It has been shown to accumulate in bone microenvironments, delivering high local concentrations of chemotherapy with reduced systemic toxicity compared to conventional treatments. Preclinical studies in rodent models of multiple myeloma, breast cancer, and prostate cancer bone metastases demonstrated MBC-11's ability to treat bone disease and reduce cancer progression with improved survival rates and reduced pain. A pilot study in spontaneous canine osteosarcoma also showed reduction in tumor activity and pain with improved quality of life. An upcoming Phase I/IIa clinical

1. First in Class Delivery Treatment
for Cancer-Induced Bone Diseases
Adam Smith Conference
November 21-23, 2012

2. Cancer-Induced Bone Diseases
Worldwide
Incidence Incidence of Bone Metastasis
• > 10,000,000 new cancer
cases every year
• 50% to 80% of carcinoma
patients will have metastasis Prostate
Myeloma
in bone at the time of their 65-75%
death 95-100%
Lung 30-40%
Current treatment
• Conventional chemo- Breast Thyroid 60%
therapeutics can not 65-75%
accumulate in bone in
relevant concentrations
• Current therapies are only Renal 20-25%
palliative
Source: Coleman RE. Skeletal Complications of Malignancy. Cancer. 1997;80(suppl 8):1588-94.
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3. Problem and Solution
Problem
No Cure For Bone Metastasis
Inability to deliver adequate amount of drug into the bone
microenvironment
Solution
Bone targeting with drug release and accumulation in the
bone microenvironment
MBC-11 Compound
etidronate-cytarabine
Conjugate of a bisphosphonate
with osteotropic properties and
cytotoxic agent
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4. Bone delivery treatment
Proven Bone Non-Toxic Proven
Targeting Drug Linkage Drug
(bisphosphonate)
Therapeutic
Bone binding via: payloads for:
Potent Anti-resorptives  Multiple Myeloma
 Osteosarcoma
 Cancer metastasis
Binds bone in Minutes
Reduced Systemic Concentrates Therapy
Toxicity at the Disease
Localization
• Unbound compound
rapidly cleared due to Bone
charge
Reduced Risks
• Linker is benign Releases Drug in Hours
• Known Drugs
phosphate
• Known Effects
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5. IP development strategy
IP current status
US 6750340
Bisphosphonate conjugates and US 7598246
methods of making and using the СА 2443857
same EP 1383510
(GB, FR, DE)
IP portfolio development
Pre/Clinical research 2012 2013 2014
Improvement of the compound
Clinical trial
IP development
Application for Improvement compound RUS PCT National phase
Application for treatment RUS PCT National phase
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6. MBC-11 Efficacy in Rodent
Models of Bone Diseases
Multiple Myeloma – Treatment of bone disease
 Increased bone mineral density
 Increased survival rate
Breast Cancer – Prevention of bone metastasis
 Reduced incidence of bone metastasis up to 65%
 Bone structure maintained
Prostate Cancer – Treatment of bone metastasis
and pain
 Bone preservation
 Reduced pain
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7. MBC-11 Efficacy in Spontaneous
Canine Osteosarcoma
Pilot study with 7 test subjects
 Reduced tumor activity
 Reduced pain
 Reduced lameness
 Improved quality of life
Observations, events, outcome
Day 0 6 14 28 85 110
SUV 23.61 24.57 21.28 16.76 N/A N/A
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8. Proof-of-Concept clinical trial
• Proof-of-Concept clinical trial (Phase I/IIa ) in
patients with metastatic bone disease (MBD)
associated with late-stage cancers and relapsed /
refractory multiple myeloma (RRMM)
• 4 clinical centers
• CT objective is to determine
– safety
– dose-limiting toxicities
– maximum tolerated dose (MTD)
– pharmacokinetics (PK)
– preliminary efficacy
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9. Thank you for your attention
Osteros Biomedica
golub@osteros.ru
+7 (495) 411-69-92
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